الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Doxorubicin is a widely used chemotherapeutic agent for treatment of broad range of cancer malignancies. But, extensive investigations have reported that it has several acute and chronic side effects on many organs including the liver, kidney and heart. Recently, several studies tend to prefer the use of antioxidant medicinal plant constituents as protective and chemo preventive agents against drug-induced toxicities. Thus, the present study aims to assess the preventive effects of navel orange peel extract and naringin on doxorubicin-induced toxicity. To achieve this aim, the adult male albino rats used in the present study were divided into the following four groups (10 rats for each): 1- Normal group: Rats of this group were orally administered 5 ml 1% CMC/kg b.w. every other day for six weeks. 2- Doxorubicin-administered control group: Rats of this group were interaperitoneally administrated doxorubicin at dose level 2 mg/kg b.w. 2 days per week for 6 weeks. This group was also orally administered the equivalent volume of 1% CMC (5 ml/kg b.w.) every other day for six weeks. 3- Doxorubicin-administered group treated with navel orange peel ethanolic extract: Rats of this group were intraperitoneally administered doxorubicin like doxorubicin-administered control group and were also orally treated with navel orange peel ethanolic extract at dose level 50 mg/kg b.w. every other day for six weeks. 4- Doxorubicin-administered group treated with naringin: Rats of this group were intraperitoneally administered doxorubicin like doxorubicin-administered control group and were also orally treated with naringin at dose level 50 mg/ kg b.w. every other day for six weeks. Results of the present study showed that doxorubicin caused a marked elevation in serum parameters related to liver function including ALT and AST activities as well as total bilirubin level. Concomitant with these biochemical changes, remarkable histopathological alterations in liver tissue were observed in doxorubicin-administered animals including necrosis of hepatocytes, apoptosis of hepatocytes, fatty change, fibroplasia in portal tract and vacuolization. The treatment of these animals with orange peel and naringin successfully prevented most of these biochemical and histopathological changes. Concerning oxidative stress and antioxidant defense system, the elevated liver lipid peroxidation of doxorubicin-administered rats, was significantly decreased as a result of navel orange peel extract and naringin. The hepatic glutathione content and glutathione peroxidase activity were decreased in doxorubicin-administered rats and potentially increased as a result of the treatments. The doxorubicin-administration induced nephrotoxicity that was evidenced by elevations in serum creatinine, uric acid and urea levels as well as histopathological changes including focal necrosis of renal tubules associated with inflammatory cell infiltration, atrophy of glomerular truft, vacuolation and protein cast. The treatment of doxorubicin-administered rats with navel orange peel ethanolic extract or naringin decreased the elevated levels of serum creatinine, uric acid and urea levels. In addition to biochemical improvement, the histological deterioration of the kidney were ameliorated in some of the treated rats. Concerning oxidative stress and antioxidant defense system, kidney lipid peroxidation of doxorubicin administered rats was elevated significantly and decreased as a result of treatments. The kidney glutathione content was significantly improved while the kidney glutathione peroxidase activity was not significantly altered as a result of both treatments. The doxorubicin- induced cardiotoxicity was evidenced by elevations in serum CK-MB and LDH activity. The elevated serum CK-MB and LDH activities of doxorubicin-administered rats were decreased as a result of both treatments. Also, histopathological changes including focal necrosis of cardiac myocytes associated with inflammatory cells were depictedin heart in doxorubicin-administered rats. The treatment with orange peel ethanolic extract and naringin successfully prevented most of these histological alterations. The heart lipid peroxidation was increased significantly as a result of doxorubicin-administered rats. The treatment of doxorubicin-administered rats with orange peel and naringin produced a marked decrease of the elevation heart lipid peroxidation. Heart glutathione content and glutathione peroxidase activity were significantly decreased in doxorubicin-administered rats while the treatment with navel orange peel induced an enormous increase. Conclusion: The co-administration of navel orange peel ethanolic extract and naringin potentially prevented the deleterious effects of doxorubicin-induced toxicity in liver, kidney and heart. This improvement effect in organs injury may be mediated via enhancement of the antioxidant defense system. However, further clinical studies are required to assess the efficacy and safety of navel orange peel ethanolic extract and naringin in human beings.